Numerous studies have shown that interleukin 1 (IL1), a cytokine secreted by macrophages, is capable of stimulating the hypothalamo‐pituitary‐adrenai (HPA) axis. Nevertheless, the sites involved in IL1 stimulation of the HPA axis remain, to data, subjects of controversy. In the present study, using in vivo and in vitro approaches, we tried to characterize the route by which IL1 acts on the HPA axis. In vivo, after an i.p. injection of human IL1β (1μg/rat), we measured plasma ACTH concentration, anterior pituitary (AP) ACTH content, hypothalamic (HT) corticotropin releasing factor (CRF) content, and also AP pro‐opiomelanocortin (POMC) and HT CRF gene expression. ACTH and CRF were measured by specific radioimmunoassays (RIAs), and solution hybridization nuclease protection assay was used for quantification of nuclear POMC precursor RNA and nuclear and cytoplasmic POMC and CRF mRNA. Human IL1β provoked an increase in ACTH plasma concentration, a decrease in AP ACTH content, and a prolonged increase in AP POMC primary transcript levels (around 100%). A significant increase in APPOMC primary transcript content was evident 30 min after injection of hIL1β, while cytoplasmic POMC mRNA levels were increased in the AP only at 4 hr after injection of hIL1β. We did not observe an effect of hIL1β on either HT CRF content or HT CRF cytoplasmic mRNA levels. In order to characterize a possible direct effect of hIL1β; at the Ap level, we used an AP perifusion system to analyse the effect of hIL1β; and CRH on ACTH release and on POMC gene expression. CRF (10−9M) applied as a 10‐minpulse provoked a marked rise in ACTH release and an 80% increase (P < 0.05) in POMC primary nuclear RNA transcript. Treatment of AP with hIL1β; (10−9M or 10−10) for 60 min did not affect ACTH release or POMC primary nuclear RNA transcript levels. The present study would suggest that the acute effect of hIL1β on ACTH secretion and synthesis is probably not due to a direct action of hIL1β at the AP level, but could result from a direct or indirect effect of IL1β on the release and synthese of hypothalamic CRF. Wiley‐Liss, Inc.
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience